Employing methods of DNA-mediated gene transfer, we propose to define and analyze Epstein-Barr virus genes which play important biologic roles in the processes of latency, viral replication and lymphocyte immortalization. We have recently found that unusual forms of EBV DNA, resembling herpes virus "defective" DNA, seem to be responsible for interrupting latency and activating the viral genome. We plan to define the structure and examine the biologic function of this "heterogeneous" DNA. We have identified a second EB nuclear antigen encoded or induced by the Bam HI M fragment. We will define the limits of this gene and identify polypeptides which are its products. We will locate, by means of gene transfer techniques, EBV genome regions which encode viral membrane antigens, early antigens and capsid antigens. We will continue efforts to describe portions of EBV DNA which are important in the process of lymphocyte immortalization. These efforts will include examination of the expression of selected EBV genes such as EBER's and EBNA's during the course of immortalization. We shall attempt to transform both lymphoid and other differentiated cells with EBV DNA fragments. We will develop methods of transfer of foreign DNA into human lymphocytes. Taken together the studies should ultimately contribute understanding of the biologic processes which underlie the involvement of EBV with an increasing number of diverse malignant lymphoproliferative diseases of man.